There exist numerous components which must work in tandem in order to provide maximum stability and mobility to joints, especially the knee joint which, under even normal conditions, sustains a load of approximately 2-7 times the body weight of the subject. Referring to the knee joint as an example of a synovial joint, the quadriceps (front of the thigh area) and hamstrings (back of the thigh area) are the two groups of muscles that control the knee joint. Referring to FIG. 1, the three bones that form the knee joint 1 are the femur 5 (thigh bone), patella (knee cap) and tibia 10 (shinbone). The tibia resides next to the fibula 15, which begins just below the knee joint 1 and runs down the leg to the ankle. The knee joint 1 includes the articular cartilage of the adjacent bones, an inner synovial membrane (synovium), a joint capsule, along with synovial fluid within the joint space. The bones of the knee joint 1 are held in place by a number of primary and secondary ligaments. The primary ligaments being the medial collateral ligament 20 (MCL; connecting the femur to the tibia on the inside of the knee joint), the lateral collateral ligament 25 (LCL; connecting the femur to the fibula on the outside of the knee), the anterior cruciate ligament 35 (ACL; connecting the femur to the tibia deep within the center of the knee joint space), the posterior cruciate ligament 30 (PCL; also located deep within the knee, and as with the ACL, also connecting the femur and tibia), and the patellar ligament (connecting the patella to the tibia). The bones of the knee joint 1 are lined with articular cartilage, which absorb shock, protects these bones, and allows the knee to move in a fluid motion. Additional cartilage is found in the form of the medial meniscus 40 and lateral meniscus 45. Both menisci are comprised of a fibrous cartilage and are located on each side of the knee on the top of the tibial plateau, absorbing the shear forces associated with normal stress associate with the knee joint.
There are a plethora of joint traumas or acute or chronic disorders associated with the synovial joints which require therapeutic intervention. Often times such traumas and disorders coincide with a substantial inflammatory response and/or persistent pain radiating from the joint area. Thus, inflammation can be an acute response to trauma or a chronic response to the presence of inflammatory agents brought about by any number of processes or events which trigger tissue damage within the knee joint. For example, when tissues are damaged, TNF-a attaches to cells to cause them to release other cytokines that cause inflammation. One type of recruited immune system cell is the macrophage. Macrophages release interleukin-1 beta (“IL-β”) and tumor necrosis factor-alpha (“TNF-a”), pro-inflammatory cytokines heavily involved in orchestrating the immediate and local physiological effects of injury or infection. For instance, once released, pro-inflammatory cytokines promote inflammation. The purpose of the inflammatory cascade is to promote healing of the damaged tissue, but once the tissue is healed the inflammatory process does not necessarily end. Left unchecked, this can lead to degradation of surrounding tissues and associated chronic pain. Thus, pain can become a disease state in itself. That is, when this pathway is activated, inflammation and pain ensue. Cycles of inflammation and associated pain often times set in. There are numerous examples of conditions in which this cycle is present including, but not limited to, conditions related to a trauma or acute or chronic disorder associated with the knee joint.
As noted above, and as an example, TNF-a inhibitors have been developed for therapeutic use to treat a knee joint trauma or disorder, such as rheumatoid arthritis and osteoarthritis. TNF-a inhibitors currently in use are generally administered systemically via intravenous infusion and subcutaneous injection, but there are side effects of anti-TNF therapies associated with the higher doses and systemic administration that are common with these therapies. In the case of direct injection, a bolus of the pharmaceutical agent is injected as near to the target site as placement of a needle will allow. Unfortunately, it provides a limited quantity of agent that must move through the tissue to the target site. Such methods are inadequate to serve the needs of patients. Anti-TNF therapy is generally needed over an extended period of time, so repeated injections are likely to be necessary. Injection site pain and reactions sometimes develop with anti-TNF-a agents. What is needed is a system and method for controlled and directed delivery of a biological agent, such as TNF-a inhibitors, for the treatment and prevention of inflammation and pain, capable of being delivered for an extended period of time at, or in close proximity to, a targeted site such as the site of trauma or inflammation.
Despite current knowledge in the field covering the surgical and non-surgical treatment of inflammation, traumas and/or disorders of joints, there remains a need for improved methods of treating acute and chronic inflammation and/or pain associated with recovery from, treatment or prevention of these disorders. The methods of the present invention address and meet these needs by disclosing methods of treating inflammation and/or pain associated with, but not limited to, the knee joint. These methods include minimally invasively or surgically delivering and tethering pharmaceutical depot implant containing a formulated biological agent within the knee joint, or any joint for that matter, so as to provide for sustained-release of the respective biological agent while maintaining normal joint articulation, thus maximizing pain relief and prospects of recovery for the subject.